Manufacturing of large scale or commercial quantities of therapeutically useful targeted biomaterials, such as proteins, can be accomplished by growing cells that are engineered to produce a desired protein in bioreactors under controlled conditions. The technology used involves, for example, the fermentation of microorganisms which have been altered through recombinant DNA techniques or the culturing of mammalian cells which have been altered through hybridoma techniques. The cells are suspended in a broth which contains the salts, sugars, proteins, and various factors necessary to support the growth of particular cells. The desired product may be either secreted by the cells into the broth or retained within the cell body. The harvested broth is then processed to recover, purify, and concentrate the desired product.
The separation, or purification, of these targeted biomaterials from a heterogeneous mixture has proven to be a formidable task for at least the following reasons: the desired product often represents a small percentage of total cell culture fluid, which comprises significant quantities of particulate and soluble contaminants, and the cell culture fluid can comprise high salt concentrations.
As a result of these factors, extensive downstream processing has been necessarily used to yield high quantities of purified product. Such downstream processing includes the many stages of processing that take place subsequent to the production of the targeted biomaterial including, for example, centrifugation, cell disruption, mechanical sieving, microfiltration, ion-exchange, cross-flow filtration, affinity separation, sterilization, purification, and packaging. The downstream processing represents a major cost in the production of bioprocessed products.
Various filtration articles have been described for the purification or separation of targeted biomaterials from fluid mixtures. U.S. Pat. Publ. No. 2011/0207196 (Koehler et al.) describes a depth filter layer with an inorganic double hydroxide layer for retaining contaminants such as DNA, while proteins of biotechnological processes are transmissible therethrough. U.S. Pat. No. 5,567,615 (Degen et al.) describes an affinity separation method involving dynamic filtration said to be particularly useful in the isolation of biologically active compounds. U.S. Pat. Publ. No. 2012/0252091 (Rasmussen et al.) describes a substrate grafted with a polymer that has affinity for binding neutral or negatively charged biomaterials.